Methods of reducing extravasation of inflammatory cells

a technology of inflammatory cells and extravasation, which is applied in the direction of biocide, drug composition, peptide/protein ingredients, etc., can solve the problems of damage to normal tissue, further impair tissue function, and unadjusted inflammatory process, so as to achieve the effect of altering the extravasation of cells associated with the extravasation

Active Publication Date: 2011-10-27
ACORDA THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0017]It has been found that the use of enzymes capable of cleaving chondroitin sulfate proteoglycans are effective in altering the extravasation of cells associated with inflammation, such as macrophages from blood vessels into tissue.

Problems solved by technology

However, the powerful inflammatory response has the capacity to cause damage to normal tissue, and dysregulation of the innate or acquired immune response is involved in different pathologies.
In many diseases such as arthritis, inflammatory bowel disease, and asthma, the inflammatory process is not appropriately regulated.
As a result, significant tissue dysfunction (leading to the generation of the symptoms that typify these diseases), and tissue re-structuring occur (e.g., fibrosis) that can further impair tissue function.
However, inflammation is more often associated with pain, injection and diseased states.
The inflammatory process inevitably causes tissue damage and is accompanied by simultaneous attempts at healing and repair.
The result can be more damage to the body than the agent itself would have produced.
In many of these cases, the problem is made worse by the formation of antibodies against self antigens or persistent antigens from smoldering infections.
Several of these therapies carry a severe risk of allowing infections to develop.
In fact, the more powerful the anti-inflammatory agents (e.g., glucocorticoids), the greater the risk of infection.
Additionally, increased mitosis in response to inflammation puts more cells at risk of mutations as they replicate their DNA during S phase.
Interfering with one or more of these signals or receptors disrupts the recruitment of inflammatory cells to the tissue.

Method used

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  • Methods of reducing extravasation of inflammatory cells
  • Methods of reducing extravasation of inflammatory cells
  • Methods of reducing extravasation of inflammatory cells

Examples

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example 1

[0076]Toxicity Studies. Female Long Evans rats from Charles River Laboratories, weighing approximately 210 grams were housed in the Acorda Animal Care Facility for 5 days prior to injection to ensure health and weight stability. Rats were anesthetized with isoflurane and injected i.v. via tail veins with chondroitinase ABC I (Seikagaku; Cat number 100332, lot number E02201). Animals were injected with either 0, 0.2, 0.775 or 7.775 mg / kg with solutions containing 0, 0.2, 0.775 and 7.775 mg / ml, respectively in Hank's balanced salt solution.

[0077]Additionally, toxicity studies were conducted for Intrathecal (IT) catheter administration. Intrathecal catheters were placed in 16 normal, un-injured female rats at about the T13 / L1 vertebral junction for delivery of chondroitinase. Catheters were fed rostrally to rest at the T9 / T10 level to simulate previous chondroitinase studies. Twenty-four hours after intrathecal catheter placement animals were dosed with 0, 0.06, 0.6 or 6.0 Units of Aco...

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Abstract

A method for modifying access of cells to extravascular spaces and regions comprising administering to a patient an enzyme that cleaves chondroitin sulfate proteoglycans is provided. It has been found that administration of an enzyme that cleaves chondroitin sulfate proteoglycans to a patient disrupts extravasation of cells from the blood stream into tissue. The present invention provides methods of reducing penetration of cells associated with inflammation into tissue of a patient. Several methods are also provided for the regulation and suppression of inflammation comprising administering enzymes that digest chondroitin sulfates. Also provided are methods of treating and preventing inflammation associated with infection, injury and disease.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application of pending U.S. application Ser. No. 10 / 847,636, filed May 17, 2004, which claims priority to U.S. Provisional Application No. 60 / 471,189, filed May 16, 2003, each of which are herein incorporated by reference in their entirety.BACKGROUND[0002]1. Field of the Invention[0003]The present disclosure relates to methods of reducing penetration of inflammatory cells into tissue, in particular to methods of reducing extravasation of macrophage cells from blood vessels, methods of preventing, regulating and suppressing inflammatory response, and methods of treating inflammatory states.[0004]2. Description of Related Art[0005]The inflammatory response evolved to protect organisms against injury and infection. Following an injury or infection, a complex cascade of events leads to the delivery of blood-borne leukocytes to sites of injury to kill potential pathogens and promote tissue repair. However, the ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/14A61P29/00A61K38/46A61K38/47
CPCA61K38/51A61K38/47A61P29/00C12N5/0006C12N5/0634C12N5/0642C12N5/0645
Inventor GRUSKIN, ELLIOTT A.TSENG, JACK L.CAGGIANO, ANTHONY O.
Owner ACORDA THERAPEUTICS INC
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